Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

Pyruvate carboxylase deficiency type A and type C: Characterization of 5 novel pathogenic variants in PC and analysis of the genotype-phenotype correlation.

MPG-Autoren
/persons/resource/persons32617

Gapsys,  V.
Research Group of Computational Biomolecular Dynamics, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons14970

de Groot,  B.
Research Group of Computational Biomolecular Dynamics, MPI for biophysical chemistry, Max Planck Society;

Externe Ressourcen
Es sind keine externen Ressourcen hinterlegt
Volltexte (beschränkter Zugriff)
Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.
Volltexte (frei zugänglich)

3034191.pdf
(Verlagsversion), 2MB

Ergänzendes Material (frei zugänglich)

3034191_Suppl_1.pdf
(Ergänzendes Material), 247KB

3034191_Suppl_2.mp4
(Ergänzendes Material), 52MB

3034191_Suppl_3.pdf
(Ergänzendes Material), 188KB

Zitation

Coci, E. G., Gapsys, V., Shur, N., Shin‐Podskarbi, Y., de Groot, B., Miller, K., et al. (2019). Pyruvate carboxylase deficiency type A and type C: Characterization of 5 novel pathogenic variants in PC and analysis of the genotype-phenotype correlation. Human Mutation, 40(6), 816-827. doi:10.1002/humu.23742.


Zitierlink: https://hdl.handle.net/21.11116/0000-0003-3282-1
Zusammenfassung
Pyruvate carboxylase deficiency (PCD) is caused by bi-allelic mutations of the PC gene. The reported clinical spectrum includes a neonatal form with early death (type B), an infantile fatal form (type A), and an late onset form with isolated mild intellectual delay (type C). Apart from homozygous stop-codon mutations leading to type B PCD, a genotype-phenotype correlation has not otherwise been discernible. Indeed, patients harboring bi-allelic heterozygous variants leading to PC activity near zero can present either with a fatal infantile type A or with a benign late onset type C form. In this study, we analyzed six novel patients with type A (three) and type C (three) PCD, and compared them with previously reported cases. Firstly, we observed that type C PCD is not associated to homozygous variants in PC. In-silico modeling was used to map former and novel variants associated to type A and C PCD, and to predict their potential effects on the enzyme structure and function. We found that variants lead to type A or type C phenotype based on the destabilization between the two major enzyme conformers. In general, our study on novel and previously reported patients improves the overall understanding on type A and C PCD.